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pmid:33833525

Identification of Metabolic-Associated Genes for the Prediction of Colon and Rectal Adenocarcinoma.

Yanfen Cui · Baoai Han · He Zhang · Hui Liu · Fei Zhang · Ruifang Niu

OncoTargets and therapy · 2021 doi:10.2147/OTT.S297134

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complete

Experiment

partial

Data

partial

Analysis

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title
Identification of Metabolic-Associated Genes for the Prediction of Colon and Rectal Adenocarcinoma.
doi
10.2147/OTT.S297134
pmid
33833525
authors array · 6 items
[0]
Yanfen Cui
[1]
Baoai Han
[2]
He Zhang
[3]
Hui Liu
[4]
Fei Zhang
[5]
Ruifang Niu
journal
OncoTargets and therapy
year
2021
abstract
BACKGROUND AND AIM: Uncontrolled proliferation is the most prominent biological feature of tumors. In order to rapidly proliferate, tumor cells regulate their metabolic behavior by controlling the expression of metabolism-related genes (MRGs) to maximize the utilization of available nutrients. In this study, we aimed to construct prognosis models for colorectal adenocarcinoma (COAD) and rectum adenocarcinoma (READ) using MRGs to predict the prognoses of patients. METHODS: We first acquired the gene expression profiles of COAD and READ from the TCGA database, and then utilized univariate Cox analysis, Lasso regression, and multivariable Cox analysis to identify the MRGs for risk models. RESULTS: Eight genes (CPT1C, PLCB2, PLA2G2D, GAMT, ENPP2, PIP4K2B, GPX3, and GSR) in the colon cancer risk model and six genes (TDO2, PKLR, GAMT, EARS2, ACO1, and WAS) in the rectal cancer risk model were identified successfully. Multivariate Cox analysis indicated that these two models could accurately and independently predict overall survival (OS) for patients with COAD or READ. Furthermore, functional enrichment analysis was used to identify the metabolism pathway of MRGs in the risk models and analyzed these genes comprehensively. Then, we verified the prognosis model in independent COAD cohorts (GSE17538) and detected the correlations of the protein expression levels of GSR and ENPP2 with prognosis for COAD or READ. CONCLUSION: In this study, 14 MRGs were identified as potential prognostic biomarkers and therapeutic targets for colorectal cancer.
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Experimentally Derived Metastasis Gene Expression Profile Predicts Recurrence and Death in Colon Cancer Patients
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Clinicopathological Parameters of COAD Patients in the TCGA Database
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Clinicopathological Parameters of COAD and READ Patients
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Clinicopathological Parameters of COAD and READ Patients
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application/vnd.jats.table+json
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verified
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read_table
reader_status
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identifier
section[14]/table-wrap[1]#t0003
version
null
note
Lasso Cox Analysis for colon cancer
structure object · 5 fields
pmcid
PMC8020594
section_index
14
section_title
Construction and Verification of the COAD Risk Model
row_count
9
column_count
4
table object · 8 fields
label
Table 3
caption
Lasso Cox Analysis for colon cancer
rows array · 9 items
[0] array · 4 items
[0]
Gene
[1]
Full Name of Gene
[2]
Coefficient
[3]
Metabolism-Related KEGG PAthways
[1] array · 4 items
[0]
ENPP2
[1]
Ectonucleotide pyrophosphatase/phosphodiesterase 2
[2]
0.0415
[3]
Ether lipid metabolism
[2] array · 4 items
[0]
GPX3
[1]
Glutathione peroxidase 3
[2]
0.0069
[3]
Glutathione metabolism
[3] array · 4 items
[0]
CPT1C
[1]
Carnitine O-palmitoyltransferase 1
[2]
0.0889
[3]
Fatty acid degradation
[4] array · 4 items
[0]
PLA2G2D
[1]
Phospholipase A2 group IID
[2]
0.0145
[3]
Glycerphospholipid metabolism; Ether lipid metabolism
[5] array · 4 items
[0]
GAMT
[1]
Guanidinoacetate N-methyltransferase
[2]
0.0957
[3]
Glycine, serine and threonine metabolism
[6] array · 4 items
[0]
PIP4K2B
[1]
Phosphatidylinositol-5-phosphate 4-kinase type 2 beta
[2]
0.0552
[3]
Inositol phosphate metabolism
[7] array · 4 items
[0]
PLCB2
[1]
Phospholipase C beta 2
[2]
0.1001
[3]
Inositol phosphate metabolism
[8] array · 4 items
[0]
GSR
[1]
Glutathione metabolism
[2]
−0.0179
[3]
Glutathione metabolism
locator
section[14]/table-wrap[1]#t0003
[5] object · 16 fields
id
asset:table:pmid:33833525:4
role
table
format
jats-table
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application/vnd.jats.table+json
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null
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sha256:b5c4a9c66b672b48b575fb7ce9a13205955386cf8494b40a875363af37ad977d
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725
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read_table
reader_status
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identifier
section[15]/table-wrap[1]#t0004
version
null
note
Lasso Cox Analysis for rectal cancer
structure object · 5 fields
pmcid
PMC8020594
section_index
15
section_title
Construction of the READ Risk Model
row_count
7
column_count
4
table object · 8 fields
label
Table 4
caption
Lasso Cox Analysis for rectal cancer
rows array · 7 items
[0] array · 4 items
[0]
Gene
[1]
Full Name of Gene
[2]
Coefficient
[3]
Metabolism-Related KEGG Pathways
[1] array · 4 items
[0]
TDO2
[1]
Tryptophan 2,3-dioxygenase
[2]
0.1041
[3]
Tryptophan metabolism
[2] array · 4 items
[0]
PKLR
[1]
Pyruvate kinase isozymes R/L
[2]
0.1239
[3]
Pyruvate metabolism
[3] array · 4 items
[0]
GAMT
[1]
Guanidinoacetate N-methyltransferase
[2]
0.0211
[3]
Glycine, serine and threonine metabolism
[4] array · 4 items
[0]
EARS2
[1]
Glutamyl-tRNA synthetase 2
[2]
−0.2970
[3]
Porphyrin and chlorophyll metabolism
[5] array · 4 items
[0]
ACO1
[1]
Aconitase 1
[2]
−0.2775
[3]
TCA cycle
[6] array · 4 items
[0]
WARS
[1]
Tryptophanyl-tRNA synthetase
[2]
−0.0097
[3]
Aminoacyl-tRNA biosynthesis
locator
section[15]/table-wrap[1]#t0004
gaps array · 2 items
[0]
asset:data:geo:GSE17538 not downloaded
[1]
asset:data:geo:GSE17538 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
family
group_comparison
specific
wilcoxon
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
Wilcoxon
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
Cox regression
[2] object · 10 fields
id
method-3
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
Log Rank
[3] object · 10 fields
id
method-4
family
diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.8
band
high
quote
ROC analysis
targets array · 0 items
gaps array · 1 item
[0]
method.group_comparison_wilcoxon
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
false
required_operations array · 0 items
missing_operations array · 1 item
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group_comparison_wilcoxon
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 1 item
[0]
GSE17538
resolved_accessions array · 1 item
[0]
GSE17538
statements array · 1 item
[0]
The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
basis
The paper names GSE17538 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 0 items
assets array · 6 items
[0]
source:pmid:33833525
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data:geo:GSE17538
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asset:table:pmid:33833525:1
[3]
asset:table:pmid:33833525:2
[4]
asset:table:pmid:33833525:3
[5]
asset:table:pmid:33833525:4
steps array · 0 items
must_build object · 5 fields
dsl_operations array · 1 item
[0] object · 3 fields
operation
group_comparison_wilcoxon
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null
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readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE17538
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T19:30:47Z
independence
single_reader
evidence_check object · 2 fields
method
absent
availability
verbatim
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3
usage object · 3 fields
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29646
completion_tokens
1787
cached_tokens
528
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
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review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:33833525
type
paper
label
pmid:33833525
[1] object · 3 fields
id
source:pmid:33833525
type
manuscript
label
PMID 33833525 full text
[2] object · 3 fields
id
data:geo:GSE17538
type
dataset
label
GEO GSE17538
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:33833525
type
paper
label
pmid:33833525
[1] object · 3 fields
id
source:pmid:33833525
type
manuscript
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PMID 33833525 full text
[2] object · 3 fields
id
data:geo:GSE17538
type
dataset
label
GEO GSE17538
agent
agent:corpus-assay-engine
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activity-read-33833525
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extraction
used array · 1 item
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source:pmid:33833525
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE17538
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accession_resolution
used array · 1 item
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data:geo:GSE17538
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agent:corpus-assay-engine
agents array · 2 items
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agent:corpus-assay-engine
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software
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Corpus assay engine
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agent:minimax-reader
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MiniMax literature reader
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reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
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ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:33833525
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sha256:d55efa6bffd24c086c0b0949e8c411bc3b177b8b98eb5f69748459308307b274
fork_of
null
gaps array · 8 items
[0]
asset:data:geo:GSE17538 licence not read
[1]
asset:data:geo:GSE17538 not downloaded
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execution.not_run
[3]
method.group_comparison_wilcoxon
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group_comparison
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support_state
partial
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dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
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Wilcoxon
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assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33833525", "kind": "science-record", "revision": 7, "content_hash": "sha256:0c9be49aaadfdacff6ea80cf24a341adaa734dda496d049b5ccf2f3a1ae26823", "created_at": "2026-11-01T15:41:31Z", "updated_at": "2026-11-01T22:03:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Metabolic-Associated Genes for the Prediction of Colon and Rectal Adenocarcinoma.", "doi": "10.2147/OTT.S297134", "pmid": "33833525", "authors": ["Yanfen Cui", "Baoai Han", "He Zhang", "Hui Liu", "Fei Zhang", "Ruifang Niu"], "journal": "OncoTargets and therapy", "year": 2021, "abstract": "BACKGROUND AND AIM: Uncontrolled proliferation is the most prominent biological feature of tumors. In order to rapidly proliferate, tumor cells regulate their metabolic behavior by controlling the expression of metabolism-related genes (MRGs) to maximize the utilization of available nutrients. In this study, we aimed to construct prognosis models for colorectal adenocarcinoma (COAD) and rectum adenocarcinoma (READ) using MRGs to predict the prognoses of patients.\nMETHODS: We first acquired the gene expression profiles of COAD and READ from the TCGA database, and then utilized univariate Cox analysis, Lasso regression, and multivariable Cox analysis to identify the MRGs for risk models.\nRESULTS: Eight genes (CPT1C, PLCB2, PLA2G2D, GAMT, ENPP2, PIP4K2B, GPX3, and GSR) in the colon cancer risk model and six genes (TDO2, PKLR, GAMT, EARS2, ACO1, and WAS) in the rectal cancer risk model were identified successfully. Multivariate Cox analysis indicated that these two models could accurately and independently predict overall survival (OS) for patients with COAD or READ. Furthermore, functional enrichment analysis was used to identify the metabolism pathway of MRGs in the risk models and analyzed these genes comprehensively. Then, we verified the prognosis model in independent COAD cohorts (GSE17538) and detected the correlations of the protein expression levels of GSR and ENPP2 with prognosis for COAD or READ.\nCONCLUSION: In this study, 14 MRGs were identified as potential prognostic biomarkers and therapeutic targets for colorectal cancer.", "claims": [{"id": "claim-data-access", "statement": "The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33833525", "locator": "sections[24] \"Data Sharing Statement\" paragraph 2", "quote": "The datasets used or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33833525"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE17538"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE17538"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33833525", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/OTT.S297134", "sha256": "sha256:686b5bb622512b76374bd19c6495e4d42bc9c8f4e118145958987f95d2e148c5", "bytes": 41021, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/OTT.S297134", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8020594", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17538", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE17538", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17538", "version": null, "note": "The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM437093", "GSM437094", "GSM437095", "GSM437096", "GSM437097", "GSM437098", "GSM437099", "GSM437100", "GSM437101", "GSM437102", "GSM437103", "GSM437104", "GSM437105", "GSM437106", "GSM437107", "GSM437108", "GSM437109", "GSM437110", "GSM437111", "GSM437112", "GSM437113", "GSM437114", "GSM437115", "GSM437116", "GSM437117", "GSM437118", "GSM437119", "GSM437120", "GSM437121", "GSM437122", "GSM437123", "GSM437124", "GSM437125", "GSM437126", "GSM437127", "GSM437128", "GSM437129", "GSM437130", "GSM437131", "GSM437132", "GSM437133", "GSM437134", "GSM437135", "GSM437136", "GSM437137", "GSM437138", "GSM437139", "GSM437140", "GSM437141", 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